The goal of this project is to understand the mechanisms that underlie the development of the pancreatic islet of Langerhans into four distinct classes of cells, the alpha, beta, delta, and PP cells. Despite their common derivation and parallel development, the islet cell types are distinguished by their ability to express distinct gene products, especially the different islet peptide hormones. This project focuses on the intercellular and inter-islet regulatory networks that develop and maintain the differentiation islet cell phenotypes by regulating islet gene expression, and the potential role of these mechanisms in the pathogenesis of the two major forms of diabetes mellitus.